prostaglandin-d2 and Carcinoma--Transitional-Cell

Although PPARgamma antagonists have shown considerable pre-clinical efficacy, recent studies suggest PPARgamma ligands induce PPARgamma-independent effects. There is a need to better define such effects to permit rational utilization of these agents.. We have studied the effects of a range of endogenous and synthetic PPARgamma ligands on proliferation, growth arrest (FACS analysis) and apoptosis (caspase-3/7 activation and DNA fragmentation) in multiple prostate carcinoma cell lines (DU145, PC-3 and LNCaP) and in a series of cell lines modelling metastatic transitional cell carcinoma of the bladder (TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2).. 15-deoxy-prostaglandin J2 (15dPGJ2), troglitazone (TGZ) and to a lesser extent ciglitazone exhibited inhibitory effects on cell number; the selective PPARgamma antagonist GW9662 did not reverse these effects. Rosiglitazone and pioglitazone had no effect on proliferation. In addition, TGZ induced G0/G1 growth arrest whilst 15dPGJ2 induced apoptosis.. Troglitazone and 15dPGJ2 inhibit growth of prostate and bladder carcinoma cell lines through different mechanisms and the effects of both agents are PPARgamma-independent.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma; Carcinoma, Transitional Cell; Caspase 3; Caspase 7; Caspases; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Chromans; DNA Fragmentation; Humans; Ligands; Male; PPAR gamma; Prostaglandin D2; Prostatic Neoplasms; RNA, Messenger; Thiazolidinediones; Troglitazone; Urinary Bladder Neoplasms